SCULPTRA® Aesthetic Prescribing Information
(injectable poly-L-lactic acid) Rx only

DEVICE DESCRIPTION |  INTENDED USE / INDICATIONS
CONTRAINDICATIONS |  WARNINGS
PRECAUTIONS |  ADVERSE EVENTS
CLINICAL STUDIES |  HOW SUPPLIED |  STORAGE |  STERILITY |  INSTRUCTIONS FOR USE
PATIENT INSTRUCTIONS |  PATIENT GUIDE

The Sculptra Aesthetic implant package (i.e., lyophilized vials and syringe) are provided sterile.

Caution: Federal (USA) law restricts this device to sale by or on the order of a licensed physician or properly licensed practitioner.

Information for the use of SCULPTRA® Aesthetic is provided in this Labeling for Physicians and the Instructions for Use, as well as in Labeling for Patients. BEFORE USING SCULPTRA® Aesthetic PLEASE READ THE FOLLOWING INFORMATION THOROUGHLY. Please direct any questions to sanofi-aventis U.S. LLC Bridgewater, NJ 08807; 1-800-633-1610

DEVICE DESCRIPTION
SCULPTRA® Aesthetic is an injectable implant containing microparticles of poly-L-lactic acid (PLLA), carboxymethylcellulose (USP), non-pyrogenic mannitol (USP) and sterile water for injection (USP). SCULPTRA Aesthetic is available in 367.5 mg dose vials and is to be reconstituted prior to use by the addition of 5 mL of Sterile Water for Injection, USP (SWFI) to form a sterile non-pyrogenic suspension.

INTENDED USE / INDICATIONS
SCULPTRA Aesthetic is indicated for use in immune-competent people as a single regimen for correction of shallow to deep nasolabial fold contour deficiencies and other facial wrinkles in which deep dermal grid pattern (cross-hatch) injection technique is appropriate. (This corresponds to Wrinkle Assessment Scores (WAS) of 2 to 4 in Figure 2 and the cross-hatch injection technique presented in Figures 3–7 in the Instructions for Use Section).

CONTRAINDICATIONS
SCULPTRA Aesthetic should not be used in any person who has hypersensitivity to any of the components of SCULPTRA Aesthetic (see
DEVICE DESCRIPTION).

SCULPTRA Aesthetic should not be used in patients with known history of or susceptibility to keloid formation or hypertrophic scarring.

WARNINGS

PRECAUTIONS

ADVERSE EVENTS

Clinical trial

Controlled phase study (0–13 months)
A prospective, randomized clinical study was conducted at 10 centers in the US. Two hundred and thirty three (233), immune-competent and non-pregnant and non-breast feeding subjects with previously untreated nasolabial fold wrinkles and WAS of 2 through 4 received bilateral injections of either SCULPTRA Aesthetic or Cosmoplast in both nasolabial fold wrinkles during a maximum of 4 sessions over 9 weeks. Study treatment was planned to be stopped when the right and left nasolabial fold wrinkle reached WAS of 1 or 0, or the maximum of 4 treatment sessions were completed. Adverse events reported in subject diaries after initial treatment are summarized in Tables 1 (intensity) and 2 (duration) below. Adverse events described in the physician case reports are summarized in Table 3 below.

TABLE 1 INTENSITY OF ADVERSE EVENTS AFTER THE INITIAL TREATMENT SESSION, RECORDED IN THE 14 DAY SUBJECT DIARY
(Controlled Phase, 0–13 months)
All-Treated Population: Per subject
SCULPTRA Aesthetic
(First Treatment Session: N = 116)
Cosmoplast
(First Treatment Session: N = 117)
Severity of Adverse Eventa Severity of Adverse Eventa
Injection
Procedure
Related Event
Total
subjects
reporting
symptomsa
n (%)
Mild
n
Moderate
n
Severe
n
Miss-
ing
n
Total
subjects
reporting
symptomsa
n (%)
Mild
n
Moderate
n
Severe
n
Miss-
ing
n
a Subjects experiencing multiple episodes of a given adverse event are counted once for that event   within the most severe category.
b Subjects who reported multiple events in the "Other" category are counted only once within the    most severe category. Adverse Events reported as "Others" are headache, dry skin, skin peeling,    rash at injection, pimples, improvement of allergy symptoms, needle marks, sinus pressure,    bruising, mouth sores, tenderness and twitching of nostril.
Localized
Swelling
94 (81.0) 64 24 5 1 76 (65.0) 60 13 1 2
Localized
Tenderness
94 (81.0) 63 24 2 5 83 (70.9) 62 16 1 4
Localized
Redness
90 (77.6) 63 23 1 3 88 (75.2) 63 23 1 1
Post-Injection
Site Pain
82 (70.7) 58 16 1 7 65 (55.6) 50 7 1 7
Localized
Bruising
75 (64.7) 44 22 6 3 50 (42.7) 26 18 1 5
Bleeding from
Site(s)
39 (33.6) 29 3 0 7 43 (36.8) 33 5 0 5
Localized
Itching
23 (19.8) 14 1 0 8 34 (29.1) 24 6 1 3
Nodules /
papules /
lumps
4 (3.4) 2 1 0 1 14 (12.0) 4 7 1 2
Otherb 19 (16.4) 7 8 1 3 22 (18.8) 11 6 3 2
Total 113 (97.4) 48 54 11 0 110 (94.0) 61 42 5 2
TABLE 2 DURATION OF ADVERSE EVENTS AFTER THE INITIAL TREATMENT SESSION, RECORDED IN THE 14 DAY SUBJECT DIARY
(Controlled Phase, 0–13 months)
All-Treated Population: Per subject
SCULPTRA Aesthetic
(First Treatment Session: N = 116)
Cosmoplast
(First Treatment Session: N = 117)
Duration of Adverse Eventa Duration of Adverse Eventa
Injection
Proced-
ure
Related
Event
Total
subjects
reporting
symptomsa
< 1
ho-
ur
1–
24
hrs
2–
7
days
8–14
days
≥15
days
Miss-
ing
Total
subjects
reporting
symptomsa
< 1
ho-
ur
1–
24
hrs
2–
7
days
8–14
days
≥15
days
Miss-
ing
a Subjects experiencing multiple episodes of a given adverse event are counted once for that event    within the longest duration category.
b Subjects who reported multiple events in "Other" category are counted only once within the    longest duration category. For list of adverse events categorized as "other", see table 1.
Localiz-
ed
Swelling
94 (81.0) 4 48 35 2 0 5 76 (65.0) 6 34 29 2 2 3
Localiz-
ed
Tendern-
ess
94 (81.0) 7 45 32 1 4 5 83 (70.9) 6 33 29 2 10 3
Localiz-
ed
Redness
90 (77.6) 13 50 24 0 0 3 88 (75.2) 11 25 33 3 13 3
Post-
Injection Site
Pain
82 (70.7) 21 44 14 0 1 2 65 (55.6) 16 35 8 0 4 2
Localiz-
ed
Bruising
75 (64.7) 6 11 44 7 2 5 50 (42.7) 3 12 25 9 0 1
Bleeding
from Site(s)
39 (33.6) 28 6 1 0 0 4 43 (36.8) 35 6 0 0 0 2
Localiz-
ed
Itching
23 (19.8) 9 5 6 0 0 3 34 (29.1) 5 8 13 2 4 2
Nodules /
papules /
lumps
4 (3.4) 0 0 2 0 1 1 14 (12.0) 0 0 3 0 9 2
Otherb 19 (16.4) 0 3 10 2 3 1 22 (18.8) 1 2 7 2 8 2
Total 113
(97.4)
2 24 67 10 9 1 110 (94.0) 5 18 54 5 27 1
TABLE 3 PHYSICIAN REPORTED* ADVERSE EVENTS AFTER ALL TREATMENTS REGARDLESS OF RELATIONSHIP TO THE DEVICE OCCURRING IN > 1% OF SUBJECTS
(Controlled Phase, 0–13 months)
All-Treated Population: Per subject
ADVERSE EVENTS
(MedDRA Preferred Term)
SCULPTRA Aesthetic
N = 116
N (%)
Cosmoplast
N = 117
N (%)
* Includes all subjects with nodules and papules regardless of duration
** Application site nodule is a lesion equal to or greater than to 5 mm,       typically palpable, asymptomatic and non-visible
***Application site papule is a lesions less than 5 mm, typically palpable,        asymptomatic and non-visible
injection site pain 11 (9.5) 12 (10.3)
application site nodule** 10 (8.6) 11 (9.4)
application site papule*** 10 (8.6) 4 (3.4)
nasopharyngitis 7 (6.0) 9 (7.7)
headache 5 (4.3) 4 (3.4)
injection site erythema 4 (3.4) 38 (32.5)
acne 3 (2.6) 4 (3.4)
pain 3 (2.6) 2 (1.7)
injection site dermatitis 3 (2.6) 1 (0.9)
hypertension 3 (2.6) 0 (0.0)
injection site haemorrhage 2 (1.7) 6 (5.1)
swelling 2 (1.7) 2 (1.7)
fracture 2 (1.7) 2 (1.7)
urinary tract infection 2 (1.7) 2 (1.7)
streptococcal infection 2 (1.7) 0 (0.0)
tooth abscess 2 (1.7) 0 (0.0)
syncope vasovagal 2 (1.7) 0 (0.0)
cough 2 (1.7) 0 (0.0)
injection site pruritus 1 (0.9) 12 (10.3)
sinusitis 1 (0.9) 6 (5.1)
application site dryness 1 (0.9) 5 (4.3)
influenza 1 (0.9) 5 (4.3)
injection site swelling 1 (0.9) 4 (3.4)
bronchitis 1 (0.9) 2 (1.7)
upper respiratory tract infection 1 (0.9) 2 (1.7)
injection site discoloration 0 (0.0) 2 (1.7)
injection site eczema 0 (0.0) 2 (1.7)
skin tightness 0 (0.0) 2 (1.7)

Adverse events that occurred with SCULPTRA Aesthetic at an incidence of <1%:
Acrochordon, anxiety, colitis, contusion, corneal abrasion, cyst, depression, dermatitis, eczema, gastritis, herpes simplex, hypercholesterolemia, hypersensitivity, hypothyroidism, injection site desquamation, injection site rash, lower respiratory infection, lymphadenopathy, migraine, muscle injury, muscle twitching, myalgia, osteoarthritis, osteopenia, pruritus, rheumatoid arthritis, gastroenteritis, skin burning sensation, spider vein, staphylococcal infection, stress symptoms, tooth infection, toothache, vaginal infection.

Extension Phase Study (13 to 25 months)
A total of 106 subjects treated with SCULPTRA Aesthetic in the initial 13 month study were followed for an additional 12 months (25 months total) after their last treatment. Only SCULPTRA Aesthetic-related adverse events were collected on the physician case report forms. Five new device-related adverse events were reported in three subjects: 2 subcutaneous papules (1.9%), 1 nodule (0.9%) and 2 injection site pain (0.9%).

Nodules and Papules
In the controlled clinical study the percentage of subjects with nodules and/or papules was greater after SCULPTRA Aesthetic [(17.2% (20/116)] than after the control treatment [(12.8%) (15/117)]. This reflects 8 Sculptra Aesthetic subjects who experienced nodules, 10 Sculptra Aesthetic patients who experienced papules and 2 Sculptra Aesthetic subjects who experienced both nodules and papules.

After the first SCULPTRA Aesthetic injection session, time to onset for nodules was 160 days (median) and 209 days (mean) and for papules 55 days (median) and 159 days (mean). After SCULPTRA Aesthetic injection, the duration of nodules was 100 days (median) and 180 (mean) days, for papules was 110 days (median) and 176 days (mean).

One subject with a papule required a single intralesional corticosteroid injection and the event resolved. For 3 subjects with nodules/papules, no information on outcome was available at the end of the 25 month extension phase study. For all remaining subjects, nodules/papules resolved spontaneously. None of these events were reported as a serious adverse event by the investigator.

Table 4 contains, for the SCULPTRA Aesthetic (0–25 months) and Cosmoplast (0–13 months) groups, summaries of the number of nodules and papules per baseline skin type, age group, and race stratified by baseline WAS. Summaries of the time to onset and duration of nodules and papules, stratified by baseline WAS are also presented.

TABLE 4 SUMMARY OF NODULES AND PAPULES, SCULPTRA AESTHETIC (SA) and COSMOPLAST (COS)
Baseline (Pre-Injection,
before first treatment) WAS
1 2 3 4 ALL
 
Treatment SA COS SA COS SA COS SA COS SA COS
Number of pt injected (N) 6 4 55 41 41 55 14 17 116 117
Patients with nodule 0
0%
0
0%
4
7.3%
4
9.8%
4
9.8%
6
10.9%
2
14.3%
1
5.9%
10
8.6%
11
9.4%
Patients with papule 0
0%
0
0%
7
12.7%
1
2.4%
5
12.2%
1
1.8%
0
0%
2
11.8%
12
10.3%
4
3.4%
Demographics
Patients Nodules or Papules per Fitzpatrick Skin Type
Fitzpatrick Skin Type = 1 0 0 1 0 1 0 0 1 2 1
Fitzpatrick Skin Type = 2 0 0 4 2 3 2 0 1 7 5
Fitzpatrick Skin Type = 3 0 0 4 2 2 4 2 1 8 7
Fitzpatrick Skin Type = 4 0 0 2 1 1 1 0 0 3 2
Fitzpatrick Skin Type = 5 0 0 0 0 0 0 0 0 0 0
Fitzpatrick Skin Type = 6 0 0 0 0 0 0 0 0 0 0
Patients Nodules or Papules per age group
Patients <35 y.o. 0 0 0 0 0 0 0 0 0 0
Patients 35–55 y.o. 0 0 7 5 4 4 1 1 12 10
Patients >55 y.o. 0 0 4 0 3 3 1 2 8 5
Patients Nodules or Papules per race
Caucasian 0 0 10 4 5 6 2 3 17 13
Hispanic 0 0 0 1 2 1 0 0 2 2
Black / Asian /Other 0 0 1 0 0 0 0 0 1 0
Time (days) from first device injection to start of event [median, mean, min, max]
Nodules - median days to
event onset
0 0 261 4.5 66 2 48.5 1 160 1
Nodules - mean days to
event onset
0 0 255.4 5.0 221.1 11 48.5 1 208.7 7.9
Nodules – time to onset
minimum days 0 0 1 1 1 1 1 1 1 1
maximum days 447 10 669 43 96 1 669 43
Papule - median days to
event onset
0 0 49 1 64 25 0 22 54.5 22
Papules - mean days to
event onset
0 0 130.7 1 197.8 25 0 17.7 158.7 15.8
Papules – time to onset
minimum days 0 0 4 1 1 25 0 1 1 1
maximum days 500 1 586 25 30 586 30
Event Duration, days [median, mean, min, max]
Nodule - median duration days 0 0 357 158.5 50 26 56.5 97 99.5 41
Nodule - mean duration days 0 0 315.4 196.8 118.9 31 56.5 97 180.1 97.3
Nodule duration
minimum days 0 0 22 8 4 3 18 97 4 3
maximum days 543 462 489 68 95 97 543 462
Papule - median duration days 0 0 157 45 62 6 0 16 109.5 16
Papule - mean duration days 0 0 186.1 45 161.6 6 0 17.7 175.9 20.8
Papules – duration
minimum days 0 0 9 45 8 6 0 15 8 6
maximum days 407 45 512 6 22 512 45

No significant associations were found between incidence of nodule/papules and geographic site, volume injected, number of treatment sessions, subject characteristics at baseline (Fitzpatrick skin type, age and race), or baseline WAS (pre-injection, before first treatment).

Post Marketing Surveillance

The following adverse events were received from post-marketing surveillance for SCULPTRA and SCULPTRA Aesthetic in the US and outside the US, that were not observed in the clinical trials with Sculptra Aesthetic: allergic reaction, angioedema (Quincke's edema), application site discharge, fatigue, hypersensitivity reaction, hypertrophy of skin, injection site abscess, injection site atrophy, injection site fat atrophy, injection site granuloma (including ectropion), injection site induration, lack of effectiveness, malaise, periorbital nodules, photosensitive reaction, scar and skin discoloration, skin infection (including cellulitis (facial) and staphylococcal infection), skin rash, skin roughness, skin sarcoidosis, telangiectasias, urticaria, visible nodules with or without inflammation or discoloration.

Scarring, mostly a non-serious event, has been reported in association with skin discoloration, nodules, lumps, indurations, granulomas, hyperpigmentation, hypertrophic scars, and suspicion of keloid formation. Time to onset ranged from 1 month to 24 months post-Sculptra injection and outcome ranged from 'improved' to 'on-going' at last contact.

Skin discoloration has been reported as a non-serious event, typically reported in association with lumps and nodules. It has also been reported with blanching and telangiectasias. Time to onset usually ranged from 1 month to 12 months post-injection. Outcome ranged from 'improved' to 'on-going' at last contact.

Serious adverse events have infrequently been reported. The most commonly reported serious adverse events (by MedDRA Preferred Term) were injection site nodule, granuloma, nodule, erythema, pain, inflammation, edema, hypersensitivity and pruritus. Regarding these infrequently reported adverse events the following describes serious adverse events with a frequency greater than 5 reported events:

CLINICAL STUDIES

A. Study Design

Controlled Phase Study (0–13 Months):
The safety and effectiveness of SCULPTRA Aesthetic use to correct WAS 2 (shallow) to 4 (deep) nasolabial fold wrinkles was evaluated in a randomized, multicenter, evaluator blinded, controlled study of otherwise healthy and immune-competent, as well as not pregnant or breast-feeding subjects with previously untreated nasolabial fold wrinkles and WAS of 2 through 4.

The subjects received bilateral injections of either SCULPTRA Aesthetic or Cosmoplast in both nasolabial fold wrinkles during a maximum of 4 sessions over 9 weeks. Study treatment was planned to be stopped when both nasolabial fold wrinkle reached optimal correction of WAS equal to 1 or 0, or until the maximum of 4 treatment sessions were completed.

The study subjects recorded adverse events in a subject diary after each treatment visit, and were followed by investigators at Week 3 and Months 3, 6, 9, and 13, after the last injection session. Standardized photographs were taken at screening, before each injection session and at each follow up visit.

Extension Phase Study (13–25 Months):
Study subjects who had received SCULPTRA Aesthetic were followed for safety and efficacy at months 19 and 25 after the last injection session. Standardized photographs were taken at each follow-up visit.

B. Study Endpoints

Controlled Phase Study (0–13 Months):
The primary efficacy endpoint was defined as the difference between SCULPTRA Aesthetic and control cohorts on the mean change from baseline in the WAS of the nasolabial folds at the 13 month follow-up time point as determined by the Blinded Evaluation Committee (BEC). Evaluation was based on the 6-point photo-numeric Wrinkle Assessment Scale (see INSTRUCTIONS FOR USE)

Optimal correction was defined as a WAS of 0 or 1.

Secondary effectiveness endpoints were: 1) Mean change from pre-treatment baseline in the WAS as determined by the BEC at the non-primary follow-up time points (Week 3 and Months 3, 6, 9, following the last treatment); 2) Treatment success rate defined as the proportion of patients with a photographic WAS of <2 as defined by the BEC at each follow-up time point; 3) Investigator/Subject Global Assessments (4= Excellent Improvement, 3= Much Improved, 2= Improved, 1= No Change, 0= Worse) and the Subject Satisfaction Scores (4= Excellent, 3= Very Good, 2= Good, 1= Satisfactory, 0= Not Satisfied) at each follow-up time point compared between treatments; and 4) Time to peak correction, defined as the length of time between pre-treatment baseline and the first time point at which the best score assessed by the BEC was obtained over the length of the follow up period. Degree of peak correction was also assessed.

Extension Phase Study (13–25 Months):
All secondary effectiveness endpoints described above were evaluated for the long- term extension study time points at 19 and 25 months.

C. Study Population

Controlled Phase Study (0–13 Months):
A total of 233 subjects (age 26 to 73 years) were randomized and treated. At the conclusion of 13 months 106 out of 116 SCULPTRA Aesthetic subjects and 111 out of 117 control subjects completed the controlled phase of the study. Demographics are outlined in Table 5.

Extension Phase Study (13–25 Months):
One hundred and six subjects, who had received SCULPTRA Aesthetic and completed the controlled phase study, entered the extension phase. The demographic and background characteristics of all subjects were similar to the overall population randomized in the controlled phase study.
At the end of the 25 month follow-up phase, 95 out of 106 of the subjects completed (see Table 5).

TABLE 5 STUDY POPULATION DEMOGRAPHICS
Controlled Phase Study Extension Phase
Study
SCULPTRA
Aesthetic
Cosmoplast SCULPTRA
Aesthetic
Demographic N (%) N (%) N (%)
Total study enrollment (randomized) 116 117 106
Age
  Mean (SD) 51.2 (7.8) 51.6 (8.4) 51.5 (7.9)
Gender
  Male 3 (2.6) 10 (8.5) 3 (2.8)
  Female 113 (97.4) 107 (91.5) 103 (97.2)
Race
  Caucasian 96 (92.8) 89 (76.1) 86 (81.1)
  Black 1 (0.9) 5 (4.3) 1 (0.9)
  Asian 0 1 (0.9) 0
  Hispanic 19 (16.4) 21 (17.9) 19 (17.9)
  Other 0 1 (0.9) 0
Fitzpatrick skin type
  Type I 11 (9.5) 5 (4.3) 10 (9.4)
  Type II 39 (33.6) 43 (36.8) 34 (32.1)
  Type III 44 (37.9) 48 (41.0) 41 (38.7)
  Type IV 16 (13.8) 15 (12.8) 16 (15.1)
  Type V 5 (4.3) 4 (3.4) 4 (3.8)
  Type VI 1 (0.9) 2 (1.7) 1 (0.9)
Nasolabial fold WAS before injection
  1 6 (5.2) 4 (3.4) 4 (3.8)
  2 55 (47.6) 41 (35.3) 50 (47.2)
  3 41 (35.3) 55 (47.6) 39 (36.8)
  4 14 (12.1) 17 (14.7) 13 (12.3)
Total completed 106 111 95

D. Treatments Delivered

Controlled Phase Study (0–13 Months):
Treatment was planned for one to four sessions at 3 week intervals until optimal correction (WAS = 1 or 0) was achieved or four sessions were completed. At each treatment with SCULPTRA Aesthetic, multiple deep dermal injections in cross hatch grid pattern (see Figures 3 – 7 in the Instructions for Use) of 0.1–0.2 mL SCULPTRA Aesthetic (up to a maximum of 2.5 mL per nasolabial fold per session) were performed into the left and right nasolabial folds according to product Instructions for Use. At each treatment session with control multiple mid to deep dermal injections of an average of 1.0 mL Cosmoplast per nasolabial fold per session were performed into the left and right nasolabial folds according to product Instructions for Use. Table 6 presents the amount of Sculptra Aesthetic injected as a function of baseline wrinkle severity.

TABLE 6 SUMMARY SCULPTRA AESTHETIC AND CONTROL INJECTIONS
Baseline (Pre-Injection, before first treatment) WAS 1 2 3 4 ALL
Sculpt-
ra Aesth-
etic
Cosmo-
plast
Sculpt-
ra Aesth-
etic
Cosmo-
plast
Sculpt-
Aesth-
etic
Cosmo-
plast
Sculpt-
ra Aesth-
etic
Cosmo-
plast
Sculpt-
ra Aesth-
etic
Cosmo-
plast
Number of pt injected (N) 6 4 55 41 41 55 14 17 116 117
Injection volume, mL
Session 1
n 6 4 55 41 41 55 14 17 116 117
Mean 4.4 2.7 4.0 2.8 4.2 3.3 4.0 3.5 4.1 3.1
Median 5.0 2.5 4.4 2.9 4.8 3.8 4.0 3.6 4.5 3.0
Range 2.0,5.0 2.0,4.0 1.5,5.0 1.4,4.0 1.7,5.0 0.9,6.0 2.6,5.0 1.0,6.0 1.5,5.0 0.9,6.0
Session 2
n 5 3 52 28 39 47 14 16 110 94
Mean 3.7 1.9 3.3 1.8 3.8 2.2 3.9 2.2 3.5 2.1
Median 4.0 2.0 3.5 1.8 4.0 2.0 4.0 1.9 3.8 2.0
Range 2.0,5.0 1.6,2.0 1.4,5.0 0.9,4.0 0.4,5.0 0.9,4.0 2.7,5.0 0.6,5.0 0.4,5.0 0.6,5.0
Session 3
n 4 1 32 18 35 30 14 11 85 60
Mean 3.4 3.0 3.0 1.6 3.4 2.0 4.0 2.0 3.3 1.9
Median 3.8 3.0 3.0 1.4 3.5 2.0 4.2 1.9 3.5 2.0
Range 1.6,4.5 3.0,3.0 0.8,5.0 0.8,4.0 0.9,5.0 0.5,5.0 2.0,4.6 0.6,4.0 0.8,5.0 0.5,5.0
Session 4
n 3 1 18 8 25 17 13 6 59 32
Mean 3.5 2.0 3.4 1.3 3.3 2.0 4.1 1.2 3.5 1.7
Median 3.4 2.0 3.7 1.0 3.3 2.0 4.0 1.0 3.7 2.0
Range 3.0,4.0 2.0,2.0 1.5,5.0 0.5,2.6 1.0,5.0 0.4,4.0 3.0,5.0 0.5,2.0 1.0,5.0 0.4,4.0
Total Volume
Injected, mL
Mean 11.5 5.4 9.9 5.0 12.7 6.9 15.7 7.3 11.7 6.2
Median 11.9 4.3 8.8 4.5 13.3 5.5 15.9 5.8 11.5 5.0
Range 4.7,17.9 4.0,9.0 4.5,18.2 1.6,14.0 2.8,20.0 1.8,16.0 11.7,19.0 2.7,16.0 2.8,20.0 1.6,16.0
Number of
sessions
Total Number
of Sessions
18 9 157 95 140 149 55 50 370 303
Mean Number
of Sessions
3 2.3 2.9 2.3 3.4 2.7 3.9 2.9 3.2 2.6
Range 1.0,4.0 1.0,4.0 1.0,4.0 1.0,4.0 1.0,4.0 1.0,4.0 3.0,4.0 1.0,4.0 1.0,4.0 1.0,4.0

The mean total volume injected per subject was 11.7 and 6.2 mL for SCULPTRA Aesthetic and control treatments, respectively. The mean total volume injected per session, for both nasolabial folds, for SCULPTRA Aesthetic was 3.7 mL and 2.4 mL for control. A mean number of 3.2 and 2.6 injection sessions were required for SCULPTRA Aesthetic and control subjects, respectively to achieve WAS of 1 or 0, or until the maximum of 4 treatment sessions with 3 week interval was reached in the study population.

Extension Phase Study (13–25 Months):
Of the 106 subjects who entered the extension phase study, 105 (99%) did not receive any additional SCULPTRA Aesthetic treatments after optimal correction was achieved in the controlled study. One subject in the extension phase study received one treatment session of SCULPTRA Aesthetic at month 19.

EFFECTIVENESS RESULTS:

Controlled Phase (0–13 month) and Extension Phase (13–25 Months) Study Results:

Primary Effectiveness Endpoint -
The difference between SCULPTRA Aesthetic and control cohorts on the mean change from baseline in the WAS of the nasolabial folds at the 13 month follow up time point as determined by the Blinded Evaluation Committee was predicted to be 1.0 unit.

For the intended use population, Figure 1 demonstrates the observed WAS change from pre-treatment baseline through each treatment and follow-up point, individually for pre-treatment WAS = 2, 3, and 4. Table 7 presents the WAS change from pre-treatment baseline at each time point stratified by pre-treatment baseline score.

SCULPTRA Aesthetic (N=116) demonstrated improved WAS as compared to control (N=117) in correcting the contour deficiency of shallow (W=2) to deep (W=4) nasolabial folds at 13 months follow up after a single treatment regimen of up to four sessions of 2.5 mL maximum injections to the deep dermis with 3 week intervals. During the extension phase study (19 and 25 months follow up) SCULPTRA Aesthetic (N=106) continued to demonstrate improvements in WAS.

Figure 1

Chemical Structure
TABLE 7 WAS SUMMARY AT EACH TIME POINT STRATIFIED BY BASELINE SCORE (Controlled and Extension Phase Study, 0–25 months) Intent-to-treat Population, SCULPTRA Aesthetic Subjects only
Baseline
WAS
Baseline
(Pre-
Injection)
Trt
Sessi-
on
2
Trt
Sessi-
on
3
Trt
Sessi-
on
4
Wk 3 Month
3
Month
6
Month
9
Month
13
Month
19
Month
25
 
N 6 4 3 3 5 3 5 5 4 4 4
Mean
(SE)
1.33
(0.086)
1.50
(0.245)
1.39
(0.111)
1.06
(0.147)
1.13
(0.200)
1.33
(0.289)
1.10
(0.155)
1.40
(0.201)
1.08
(0.337)
1.17
(0.180)
1.25
(0.160)
1 Medi-
an
1.42 1.58 1.50 1.00 1.33 1.33 1.17 1.50 1.25 1.25 1.33
Mean Chan-
ge from Baseli-
ne (SE)
N/A 0.17
(0.236)
-0.06
(0.056)
-0.22
(0.056)
-0.17
(0.190)
-0.11
(0.242)
-0.27
(0.113)
0.03
(0.111)
-0.25
(0.220)
-0.17
(0.068)
-0.08
(0.048)
P-Value for Chan-
ge from Baseli-
ne
N/A 0.530 0.423 0.057 0.430 0.691 0.078 0.778 0.339 0.092 0.182
 
N 55 50 27 16 48 48 48 46 48 42 44
Mean
(SE)
2.19
(0.037)
2.02
(0.060)
1.75
(0.112)
1.69
(0.147)
1.63
(0.073)
1.64
(0.070)
1.69
(0.051)
1.60
(0.063)
1.60
(0.063)
1.51
(0.082)
1.58
(0.076)
2 Medi-
an
2.17 2.00 1.83 1.92 1.67 1.67 1.83 1.50 1.67 1.50 1.58
Mean Chan-
ge from Baseli-
ne (SE)
N/A -0.17
(0.057 )
-0.46
(0.107)
-0.57
(0.145)
-0.53
(0.077)
-0.53
(0.071)
-0.50
(0.054)
-0.59
(0.062)
-0.59
(0.067)
-0.69
(0.084)
-0.61
(0.079)
P-Value for Chan-
ge from Baseli-
ne
N/A 0.005 <0.001 0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
 
N 41 38 33 21 39 34 35 36 37 36 36
Mean(SE) 2.99
(0.043)
2.64
(0.065)
2.52
(0.067)
2.21
(0.084)
2.21
(0.068)
2.13
(0.066)
2.06
(0.088)
2.03
(0.084)
1.84
(0.068)
2.08
(0.098)
2.03
(0.090)
3 Medi-
an
2.83 2.67 2.33 2.17 2.17 2.08 2.00 2.08 1.83 2.08 2.00
Mean Chan-
ge from Baseli-
ne (SE)
N/A -0.37
(0.066)
-0.52
(0.053)
-0.83
(0.085)
-0.77
(0.069)
-0.83
(0.068)
-0.94
(0.083)
-0.97
(0.078)
-1.15
(0.065)
-0.94
(0.097)
-0.96
(0.089)
P-Value for Chan-
ge from Baseli-
ne
N/A <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
 
N 14 14 13 13 11 12 11 11 13 10 9
Mean
(SE)
4.07
(0.078)
3.74
(0.107)
3.58
(0.129)
3.40
(0.166)
3.15
(0.220)
3.18
(0.168)
3.11
(0.151)
3.09
(0.196)
3.26
(0.169)
3.60
(0.161)
3.85
(0.207)
4 Medi-
an
4.08 3.67 3.67 3.33 3.17 3.17 3.17 3.00 3.17 3.75 3.83
Mean Chan-
ge from Baseli-
ne (SE)
N/A -0.33
(0.103)
-0.49
(0.112)
-0.71
(0.145)
-0.92
(0.232)
-0.94
(0.167)
-1.02
(0.138)
-0.97
(0.194)
-0.85
(0.164)
-0.53
(0.108)
-0.31
(0.168)
P-Value for Chan-
ge from Baseli-
ne
N/A 0.007 <0.001 <0.001 0.003 <0.001 <0.001 <0.001 <0.001 <0.001 0.097

HOW SUPPLIED

SCULPTRA Aesthetic is supplied as a sterile freeze-dried preparation for injection in a clear glass vial, which is sealed by a penetrable stopper, covered by an aluminum seal with a flip-off cap. Each carton of SCULPTRA Aesthetic contains two vials of poly-L-lactic acid, sodium carboxymethylcellulose (USP), non-pyrogenic mannitol (USP) NHRIC 8313-1118-02

STORAGE
SCULPTRA Aesthetic can be stored at room temperature, up to 30ºC (86ºF). DO NOT FREEZE.
Refrigeration is not required.

STERILITY
Each vial of SCULPTRA Aesthetic is packaged for single-use only. Do not resterilize.

IF THE VIAL, SEAL, OR THE FLIP-OFF CAP ARE DAMAGED, DO NOT USE AND CONTACT SANOFI-AVENTIS U.S. LLC AT 1-800-633-1610.

INSTRUCTIONS FOR USE

SCULPTRA Aesthetic has only been evaluated in immune-competent people as a single regimen for correction of shallow to deep nasolabial fold contour deficiencies and other facial wrinkles in which deep dermal grid pattern (cross-hatch) injection technique is appropriate.

SCULPTRA Aesthetic use should be limited to use in a single regimen of up to four sessions with three week interval using the threading or tunneling technique in grid pattern (see Figures 3– 7) to inject a maximum of 2.5 mL of SCULPTRA Aesthetic per site into the deep dermis medial to the nasolabial fold contour deficiency.

The following supplies are used with SCULPTRA Aesthetic but are to be provided by the end-user:

Reconstitution

SCULPTRA Aesthetic is reconstituted in the following way:

  1. Remove the flip-off cap from the vial and clean the penetrable stopper of the vial with an antiseptic. If the vial, seal, or flip-off cap is damaged, do not use, and call sanofi-aventis U.S. LLC at 1-800-633-1610.
  2. Attach an 18 G sterile needle to a sterile single-use 5 mL syringe.
  3. Draw 5 mLs of SWFI into the 5 mL syringe.
  4. Introduce the 18 G sterile needle into the stopper of the vial and slowly add all SWFI into the vial.
  5. Let the vial stand for at least 2 hours to ensure complete hydration; do not shake during this period. SCULPTRA Aesthetic can be stored at room temperature up to 30°C (86°F) during and after hydration. Refrigeration is not required.
  6. Product should be gently agitated immediately prior to use. Agitate the vial until a uniform translucent suspension is obtained. A single vial swirling agitator may be used. The reconstituted product is usable within 72 hours of reconstitution. As it is a single use vial, discard any material remaining after use or after 72 hours following reconstitution.
  7. Clean the penetrable stopper of the vial with an antiseptic, and use a new 18 G sterile needle to withdraw an appropriate amount of the suspension (typically 1 mL) into a single–use 1 or 3 mL sterile syringe. Do not store the reconstituted product in the syringe.
  8. Replace the 18 G needle with a 26 G sterile needle before injecting the product into the deep dermis. Do not inject SCULPTRA Aesthetic using needles of an internal diameter smaller than 26 G.
  9. To withdraw remaining contents of the vial, repeat steps 6 through 8.

Patient Treatment

1. Patient Counseling.
It is necessary to counsel the patient and discuss the appropriate indication, risks, benefits and expected responses to the SCULPTRA Aesthetic treatment. Advise the patient of the necessary precautions before commencing the procedure.

Chemical Structure

Figure 2

2. Patient Assessment.

3. Patient Preparation.
Each injection session is to be conducted with aseptic technique and universal precautions due to the potential for contact with patient body fluids: blood from the injection site. Before injecting SCULPTRA Aesthetic a treatment plan is determined and the face mapped. The mapping is done using a water soluble pencil and a grid that is parallel and perpendicular to the nasolabial fold is outlined. See Section 6 - Injecting: Threading or Tunneling Technique.

4. Injection Needle.
SCULPTRA Aesthetic should be injected using a sterile 26 G needle. SCULPTRA Aesthetic should not be injected with needles with a diameter smaller than 26 G or needles that have been bent. To maintain a uniform suspension throughout the procedure, intermittently agitate SCULPTRA Aesthetic in the syringe. Before initial injection, expel a few drops of SCULPTRA Aesthetic through the attached 26 G needle to eliminate air and to check for needle blockage. If the needle becomes occluded or dull during an injection session needle replacement is necessary. If clogging occurs, remove the needle, expel a small amount of product, attach a new sterile 26g needle, then expel a few drops of SCULPTRA Aesthetic to eliminate the air and re-check for needle blockage.

5. Depth of Injection.
SCULPTRA Aesthetic should be injected into the deep dermis with tunneling (threading) technique.

As per Figure 7, SCULPTRA Aesthetic should be injected into tissue that is medial to the nasolabial fold wrinkle defect.

To guide the needle to the deep dermal plane, create a firm needle insertion plane by stretching the skin (Figure 3).

Chemical Structure

Figure 3

Introduce a straight, sterile, bevel-up 26 G needle into the skin at an approximately 30–40 degree angle to the skin and then advance the needle to the deep dermis until the desired skin depth is reached (Figure 4).

Chemical Structure

Figure 4

A change in tissue resistance is felt when the needle crosses from the dermis into subcutaneous layer. If the needle is inserted at too shallow (small) an angle or if the needle tip is not sufficiently advanced, then the needle tip may be in the mid or superficial (papillary) dermis, the needle bevel may be visible through the skin. If SCULPTRA Aesthetic is injected too superficially, the injected area will blanch immediately or slightly after injection. If the injected area blanches, remove the needle and massage the area in a circular fashion. In the event that the blanching does not disappear, the patient should not be re-injected.

6. Injecting: Threading or Tunneling Technique in a Grid Pattern (cross-hatch).

a. Technique.
When the needle tip is in the deep dermal plane, the needle angle should be lowered to 10–20 degrees and the needle should be advanced in the deep dermal plane parallel to the surface of the skin (Figure 5).

Chemical Structure

Figure 5

Before injecting SCULPTRA Aesthetic, always perform a reflux maneuver to avoid intravascular injection. If blood returns to the syringe, the needle is in a blood vessel and should be withdrawn, pressure should be applied to the injected area until bleeding stops and a new syringe should be prepared. If no blood is pulled back into the syringe, use the threading or tunneling technique, to deposit a thin trail of SCULPTRA Aesthetic by doing a retrograde injection when slowly withdrawing the needle (Figure 6).

Chemical Structure

Figure 6

Based on the treatment plan (see Section 3 - Patient Preparation), Start the first injection at the base of the nasolabial fold. After completing the length with injections parallel to the nasolabial fold, the cross-hatch pattern is achieved with additional injections perpendicular to the first injection. Picture below shows a cross-hatch pattern after completing the last injection (Figure 7).

Chemical Structure

Figure 7

b. Volume per Injection.
The maximum volume of SCULPTRA Aesthetic per individual injection should be limited to 0.1 mL – 0.2 mL, spaced at a distance of 0.5 –1 cm. Avoid overcorrection.

c. Volume per Treatment Site.
A treatment session to correct WAS 2 – 4 nasolabial fold contour deficiencies consists of multiple deep dermal threading or tunneling injection of 0.1–0.2 mL of SCULPTRA Aesthetic in grid pattern to a maximum of 2.5 mL per nasolabial fold per session. The volume of SCULPTRA Aesthetic per surface area of injection grid has not been determined. During the initial treatment sessions only a limited correction should be made. In contrast to other wrinkle fillers, SCULPTRA Aesthetic provides a gradual correction of a contour deficiency over several weeks.

7. Massage During the Injection Session.
The treatment area should be massaged in a circular fashion after every 3–4 injections to evenly distribute the product.

8. Degree of Correction.
The contour deficiency should be under-corrected, never fully corrected or overcorrected (overfilled) during any injection session. Under-correction of the treatment area allows for gradual improvement of the contour deficiency as the SCULPTRA Aesthetic effect occurs over the minimum of three weeks between assessment and possible next injection session.

9. Post-treatment Care.
Immediately after a SCULPTRA Aesthetic injection session, redness, swelling, and/or bruising may appear in the treatment area. See ADVERSE EVENTS for details of the incidence and severity of adverse event observed immediately post-injection during the clinical trial. To help SCULPTRA Aesthetic distribute evenly in the contour deficiency, it is important at the end of the treatment session to manually massage in a circular fashion the treatment area for a minimum of 2 minutes. A facial moisturizer should be used to perform the massage.

It is recommended that the patient should massage the treated areas for five minutes, five times per day for five days after the injection session to promote a natural-looking correction. To reduce the risk of edema and/or bruising after injection, an ice pack (avoid any direct contact of the ice with the skin) is applied to the treated areas.

Early occurrence of subcutaneous nodules at the injection site (within 3 to 6 weeks after the treatment) may be minimized by adhering to proper dilution and injection techniques (e.g., avoiding superficial injections or over-correction). In addition, massaging the treatment area to ensure proper distribution of the product may also minimize the appearance of nodules. Nodules usually resolve spontaneously. However, as reported in published literature, some nodules may require medical treatment such as subcision (break-up of nodules with sterile saline solution), and delayed occurrence of subcutaneous nodules at the injection site (usually will manifest within 3 to 4 months after the treatment) may require treatment such as intralesional injections of corticosteroids, subcision and/or excision.

10. Treat, Wait, Assess.
During the first injection session with SCULPTRA Aesthetic, only a limited correction should be made. The contour deficiency should be under-corrected, never fully corrected or overcorrected (overfilled) during any injection session. Re-evaluate the patient no sooner than three weeks after the injection session to determine if additional correction is needed. The patient should be advised before and after an injection, that typically at the end of the injection session, it is expected to experience some degree of swelling associated with the injection procedure itself. This will give the appearance of a full correction by the end of the injection session and this injection-related swelling typically resolves in several hours to a few days. For this reason, the original contour deficiency may initially reappear, but the deficiency is expected to gradually improve within several weeks of SCULPTRA Aesthetic injection as the effect occurs. The patient should be advised of the potential need for up to four injection sessions (typically three) at the first consultation.

PATIENT INSTRUCTIONS
It is recommended that the following information is shared with patients by the healthcare provider:

ANY SIDE EFFECTS, ADVERSE EVENTS, PRODUCT QUESTIONS OR PRODUCT COMPLAINTS SHOULD BE REPORTED TO:
sanofi-aventis U.S. LLC
Bridgewater, NJ 08807
1-800-633-1610

Prescribing Information as of December 2009.

Dermik Laboratories
a business of sanofi-aventis U.S. LLC
Bridgewater, NJ 08807
1-800-633-1610

©2009 sanofi-aventis U.S. LLC

Caution: Federal (USA) law restricts this device to sale by or on the order of a licensed physician or properly licensed practitioner.

A PATIENT'S GUIDE TO TREATMENT WITH SCULPTRA® Aesthetic

SCULPTRA Aesthetic
(injectable poly-L-lactic acid)

Please review this information carefully before beginning your SCULPTRA Aesthetic Treatment.
This guide is intended to help you become familiar with SCULPTRA Aesthetic use, as well as the expected correction, method of injection, post-injection skin care and possible side effects. You may request additional information such as the product label that further describes SCULPTRA Aesthetic and its clinical data from your physician. This information is also available on www.sculptraaesthetic.com. This information is not meant to replace information provided by your healthcare provider. You should always ask your healthcare provider about your treatment and care.

GLOSSARY

Anesthetic: A substance that causes loss of feeling or awareness. A topical or local anesthetic is a drug that causes temporary loss of feeling in a part of the body where it is placed.
Antiseptic: An agent that kills bacteria or prevents or slows growth of germs.
Biocompatible: A material that does not harm the body.
Biodegradable: A material that can be broken down by the body.
Collagen: The most common protein found in the body. Collagen is used to form a framework to support cell and tissue.
Hypersensitivity: undesirable, discomfort producing reaction; or an allergic reaction.
Injection: Product delivery at the location of a hollow needle tip beneath the surface of the skin.
Immunocompetent: Has a healthy immune system
Keloid formation /Hypertrophic scarring: An overgrowth of scar tissue at the site of a skin injury. Keloids/hypertrophic scars may occur around surgical cuts, traumatic wounds, vaccination sites, burns, or minor scratches. Hypertrophic scarring commonly resolves during the first year after injury; keloid formation most commonly does not resolve.
Lipoatrophy: Loss of fat that is normally under the skin.
Nasolabial fold/ wrinkle: Lines between the nose and the corner of the mouth.
Nodule: Lump under the surface of the skin that is greater than 5 mm, may be visible or not visible, but can be felt when pressed.
Palpable: Able to be touched and felt.
Papule: Lump under the surface of the skin that is less than 5 mm and not visible, but can be felt when pressed.
Patient label: Product information for patients
Peri-orbital: Around the eye.
Poly-L-lactic acid: A man-made lactic acid polymer that is biocompatible and biodegradable.
Product label: Product information for healthcare providers
Side effect: An unwanted event caused by use of the product.
Wrinkle: age-related defect in the contour of the skin surface.
Wrinkle Assessment Score (WAS): a six point photo-numeric scale for the assessment of nasolabial fold wrinkles (see Figure 1).
Wrinkle filler: A product that is injected under the surface of skin to fill a space to decrease the appearance of a cosmetic facial contour deficiency such as facial lines, wrinkles or folds.

WHAT IS SCULPTRA AESTHETIC?
SCULPTRA Aesthetic is a sterile, injectable, biocompatible, biodegradable material that is made of very small particles of a synthetic polymer named "poly-L-lactic acid" (PLLA), carboxymethylcellulose (USP), non-pyrogenic mannitol (USP) and sterile water for injection (USP). While the time needed for SCULPTRA Aesthetic to resorb in humans is not known, in rabbits, particles were visible at over one year after injection.

WHO MIGHT BENEFIT FROM TREATMENT WITH SCULPTRA AESTHETIC?
SCULPTRA AESTHETIC is intended for use in people with healthy immune systems as one-time treatment regimen of up to 4 injection sessions that are scheduled about 3 weeks apart for correction of shallow to deep nasolabial fold contour deficiencies and other facial wrinkles in which deep dermal grid pattern (cross-hatch) injection technique is appropriate. SCULPTRA Aesthetic may provide cosmetic correction of facial wrinkles with a Wrinkle Assessment Score of 2, 3, or 4 as shown in the following photos (Figure 1):

Chemical Structure

Your healthcare provider can help you determine if you might benefit from SCULPTRA Aesthetic and the optimal cosmetic correction expected for you. In the US clinical study, optimal correction at 9 weeks after initial injection was most commonly found to be a 0.5 to 1 point decrease (improvement) in WAS.

WHO SHOULD NOT GET SCULPTRA AESTHETIC? (CONTRAINDICATIONS)
You should not get SCULPTRA AESTHETIC if you:

WHAT SHOULD I BE AWARE OF BEFORE RECEIVING SCULPTRA AESTHETIC INJECTIONS (WARNINGS AND PRECAUTIONS)?
In addition to the other information contained in this guide, you should be aware of the following:

It is unknown whether SCULPTRA Aesthetic may be seen during radiologic imaging of your face. If radiologic imaging of your face such as computer tomography (CT) or magnetic resonance imaging (MRI) is to be performed, you should notify the physician about the location of your previous SCULPTRA Aesthetic injection.

HOW DOES SCULPTRA AESTHETIC WORK?
Collagen production in the body decreases as you get older and/or are exposed to the sun. Wrinkles are one of the first visible signs of this. SCULPTRA AESTHETIC is injected into the deep layer of the skin where collagen naturally exists and is made. SCULPTRA Aesthetic works by initially filling a wrinkle with small PLLA beads. As the beads biodegrade the body may produce new collagen where SCULPTRA Aesthetic is injected. SCULPTRA Aesthetic is injected with multiple small injections using a fine needle in a grid pattern to correct a wrinkle at the nasolabial fold or other facial wrinkles where this injection technique is appropriate:

Chemical Structure

WHAT WERE THE RESULTS OF THE U.S. CLINICAL STUDY CONDUCTED ON SCULPTRA AESTHETIC?
A U.S. study was conducted to compare the safety and effectiveness of SCULPTRA Aesthetic and a control for the treatment of facial wrinkles. The treatment consisted of one to four visits at three (3) week intervals during which the 233 subjects received treatment with either SCULPTRA Aesthetic (n=116) or the control (n=117). Subjects were followed for 13 months after the last treatment. Doctors graded standardized photographs to evaluate the wrinkle reduction effectiveness of both SCULPTRA Aesthetic and the control. Safety was evaluated by comparing the number and severity of side effects during the study. Side effects are summarized in the table 1 below.

TABLE 1: NUMBER OF SUBJECTS WITH INJECTION-RELATED SIDE EFFECTS OBSERVED IN SCULPTRA AESTHETIC U.S. CLINICAL STUDY
*one subject reported mild injection site pain approximately 20 months   after first injection, no information on outcome was available at the end   of the 25 month extension phase study
SIDE EFFECTS TYPE
Immediate, as recorded in subject diaries
116 Subjects
N (%)
Localized Swelling 94 (81.0%)
Localized Tenderness 94 (81.0%)
Localized Redness 90 (77.6%)
Post-Injection Site Pain 82 (70.7%)
Localized Bruising 75 (64.7%)
Bleeding from Site(s) 39 (33.6%)
Localized Itching 23 (19.8%)
Other 19 (16.4%)
DELAYED, as reported by physicians
Nodules and papules 20 (17.2%)
Delayed injection site pain* 1 (0.9%)
Average time to appearance after first injection:
Nodules 209 days
Papules 159 days
Average time of duration:
Nodules 180 days
Papules 176 days

Most side effects were mild and resolved on their own; one small papule required treatment by the healthcare provider. Five new Sculptra-related events were reported more than 13 months after first injection with SCULPTRA Aesthetic in three subjects: 2 papules (1.9%), 1 nodule (0.9%) and 2 injection site pain (0.9%).

Results showed that SCULPTRA Aesthetic had effects lasting up to 25 months in some patients for the treatment of nasolabial fold wrinkles as compared to control. Both treatments were well tolerated.

WHAT ADVERSE EVENTS HAVE BEEN REPORTED THROUGH VOLUNTARY POST-MARKETING SURVEILLANCE OF SCULPTRA AND SCULPTRA AESTHETIC USE IN AND OUTSIDE OF THE US?

The most commonly reported serious adverse events were lumps or nodules at the injection site, delayed swollen lumps (granulomas), redness, pain, inflammation, swelling, hypersensitivity and itching. The following events were reported more than 5 times:

Other events that were reported included: application site discharge, fatigue, hypertrophy of skin, injection site atrophy, injection site hardness (induration), lack of effectiveness, malaise, photosensitive reaction, scar, skin discoloration, skin rash, skin roughness, skin disease inflammation (skin sarcoidosis), skin whitening at the injection site, dilated small blood vessels (telangiectasias), hives (urticaria), visible lumps with or without inflammation or discoloration.

ARE SKIN TESTS NEEDED BEFORE TREATMENT WITH SCULPTRA AESTHETIC?
No skin testing is required prior to use in immunocompetent people with skin that heals normally

ARE THE RESULTS FROM SCULPTRA AESTHETIC IMMEDIATE?
No. Unlike other wrinkle fillers, SCULPTRA Aesthetic provides a gradual improvement of the depressed area over several weeks as the treatment effects occur. During the initial treatment session with SCULPTRA Aesthetic, a contour defect should be under-corrected, not fully-corrected or over-corrected. It may seem that your treatment worked immediately because of swelling caused by injection and the water used to dilute SCULPTRA Aesthetic. This usually resolves in several hours to a few days and may cause the original wrinkle to reappear: you may look as you did before your treatment. Visible wrinkle correction results appear slowly. Your healthcare provider should see you again in three or more weeks to decide if you need additional injections.

HOW OFTEN ARE SCULPTRA AESTHETIC TREATMENTS GIVEN AND HOW MANY TREATMENTS ARE REQUIRED?
Your healthcare provider should see you at approximately three week after each treatment session to assess whether you need additional treatment. You may need one to four treatment sessions (typically three) to achieve the optimal correction possible. The safety and effectiveness of SCULPTRA Aesthetic has only been studied in a single treatment regimen of up to four sessions at three week intervals.

HOW LONG DO SCULPTRA AESTHETIC TREATMENT EFFECTS LAST?
In a U.S. clinical study treatment results for some subjects lasted for up to 25 months after the last treatment session. However, the improvement depended on the severity of the nasolabial fold wrinkle (WAS score) that a subject had before treatment. Discuss with your health care provider the optimal cosmetic correction you may expect.

DO INJECTIONS OF SCULPTRA AESTHETIC HURT?
As with any injection, to decrease pain during injection, a topical or a local anesthetic may be applied to the injection area skin before injecting SCULPTRA Aesthetic. In U.S. clinical study, subjects recorded pain in diaries: 71% of all treated patients reported some pain after first injection, 14% of subjects had moderate pain. Most pain resolved in less than 24 hours.

WHAT CAN I EXPECT TO HAPPEN AT A TREATMENT SESSION?
Your healthcare provider will answer all of your questions and ask about your medical history to determine if SCULPTRA Aesthetic injection is appropriate for you. Tell your healthcare provider about all the medicines you are taking, even over the counter medicines or treatments. You and your healthcare provider will determine if a topical or local anesthetic is needed.

WHAT CAN I EXPECT AFTER TREATMENT?
Immediately following a treatment session with SCULPTRA AESTHETIC, redness, swelling, pain, bruising or all of these signs can happen in the treatment area. These signs usually go away in a few hours to a few days. Some have been known to last more than 14 days. Your healthcare provider will give you specific post-treatment care instructions. Some specific instructions you should follow after treatment are:

HOW QUICKLY CAN I GET BACK TO MY DAILY ACTIVITIES?
Most patients are able to get back to their activities immediately following treatment.

WHEN WILL I BE ABLE TO APPLY MAKE-UP AFTER TREATMENT?
Make-up may be applied a few hours after treatment if there are no complications such as open wounds or bleeding.

WHAT ARE MY OTHER OPTIONS FOR TREATMENT?
There are a variety of dermal fillers available in the US. Prices, safety and effectiveness vary. Consult with your physician to determine which one is right for you.

FOR FURTHER QUESTIONS AND INFORMATION, OR TO REPORT ANY SIDE EFFECTS, PLEASE CALL SANOFI-AVENTIS AT 1-800-633-1610

Patient Prescribing Information as of December 2009.
Dermik Laboratories
A business of sanofi-aventis U.S. LLC
Bridgewater, NJ 08807


POL-A-WFSPLW-WEBW-DEC09